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羧胺三唑对TNF-α诱导的成纤维样滑膜细胞增殖及MMP-1、MMP-3表达的影响
  • ISSN号:1674-0785
  • 期刊名称:中华临床医师杂志(电子版)
  • 时间:2013.5.15
  • 页码:4354-4357
  • 分类:R593.22[医药卫生—临床医学;医药卫生—内科学]
  • 作者机构:[1]中国医学科学院基础医学研究所北京协和医学院基础学院药理系,100005
  • 相关基金:国家自然科学基金(81102454);"重大新药创制"科技重大专项(2009ZX09102-049);中国医学科学院院所长基金(2010PY01,2010PY08)
  • 相关项目:炎症体介导实验性关节炎滑膜细胞活化的病理机制及羧胺三唑的治疗作用
中文摘要:

目的 研究羧胺三唑(CAI)对TNF-α诱导的佐剂性关节炎大鼠成纤维样滑膜细胞(FLS)增殖以及MMP-1、MMP-3表达的影响.方法 用弗氏完全佐剂诱导大鼠佐剂性关节炎模型,并分离培养佐剂性关节炎大鼠的FLS.实验分为对照组,20 ng/ml TNF-α组,同时加入TNF-α和溶剂DMSO组,以及同时加入NF-α和不同浓度CAI(10、20、40 μmoL/L)组.CCK-8法检测FLS的增殖反应,Western blot法检测MMP-1和MMP-3的蛋白表达.结果 20 ng/mlNF-α能明显增加佐剂性关节炎大鼠FLS的增殖反应,增加MMP-1和MMP-3的蛋白表达(P<0.01).CAI(20、40 μmol/L)能够显著抑制TNF-α对佐剂性关节炎大鼠FLS的促增殖反应(P<0.01),抑制率分别为(31.13±7.07)%和(42.48±5.84)%,且CAI能够降低TNF-α诱导的MMP-1和MMP-3产生(P<0.01).结论 CAI体外给药能够抑制TNF-α诱导的佐剂性关节炎大鼠FLS增殖以及产生MMP-1和MMP-3,这可能是其抗关节炎作用的机制之一.

英文摘要:

Objective To investigate the effects of carboxyamidotriazole(CAI) on the proliferation and the expressions of MMP-1 and MMP-3 in TNF-α-induced fibroblast-like synoviocytes(FLS) from adjuvant arthritis(AA) rats.Methods Freund's completed adjuvant was used to induce AA in rats,and FLS were separated and cultured from AA rats.AA FLS were stimulated by 20 ng/ml TNF-α with or without the vehicle DMSO or CAI (10,20,40 μmol/L)for 24 h,and the unstimulated group incubated only by the fresh medium was used as the control group.FLS proliferation was determined by CCK-8 method,and the protein expressions of MMP-1 and MMP-3 were measured by Western blot.Results The proliferation of FLS and the expressions of MMP-1 and MMP-3 were significantly increased under TNF-α stimulation(P 〈0.01).CAI(20,40 μ mol/L)treatment suppressed the elevated proliferation of FLS stimulated by TNF-α (P 〈 0.01),and the inhibition ratios were (31.13 ± 7.07) % and (42.48 ±5.84)%,respectively.In addition,CAI (20,40 μmol/L)inhibited MMP-1 and MMP-3 expressions in TNF-α-stimulated FLS(P〈0.01).Conclusion CAI can inhibited TNF-α-induced proliferation and MMP-1 and MMP-3 productions in AA FLS which might be one of its anti-arthritic mechanisms.

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期刊信息
  • 《中华临床医师杂志(电子版)》
  • 主管单位:
  • 主办单位:中华医学会
  • 主编:
  • 地址:北京市西直门北大街32号B座606C室
  • 邮编:100082
  • 邮箱:lcdoctor@163.com
  • 电话:010-62219211
  • 国际标准刊号:ISSN:1674-0785
  • 国内统一刊号:ISSN:11-9147/R
  • 邮发代号:
  • 获奖情况:
  • 国内外数据库收录:
  • 美国化学文摘(网络版),波兰哥白尼索引
  • 被引量:30430